Patients

The characteristics of patients, including demographic data, indications for the CIED procedure, comorbidities, and indications for and the type of chronic antiplatelet therapy (APT) or anticoagulant therapy (ACT), as well as procedural details for postimplant wound management were collected at the time of the CIED surgery. All comorbidities were diagnosed according to the current guidelines of the relevant international societies, and the appropriate treatment recorded in the documentation confirmed the diagnosis of a specific diseases. However, it should be emphasized that uncontrolled arterial hypertension was diagnosed when systolic blood pressure was at least 160 mm Hg and/or diastolic blood pressure was at least 100 mm Hg on 2 or more independent measurements during hospitalization. Patients were divided into 4 main groups: 1) ACT group (vitamin K antagonist [VKA] in doses dependent on the international normalized ratio [INR] level, direct oral anticoagulant [DOAC], or low‑molecular‑weight heparin [LMWH]); 2) APT group (single antiplatelet therapy [SAPT] with aspirin or clopidogrel at a dose of 75 mg/d or double antiplatelet therapy [DAPT] with aspirin [75 mg/d] and clopidogrel [75 mg/d], or aspirin [75 mg/d] and ticagrelor [180 mg/d], or aspirin [75 mg/d] and prasugrel [10 mg/d]); 3) triple antithrombotic therapy (TAT) group (DAPT with VKA or DOAC); and 4) control group (patients not receiving ACT or APT). Moreover, the ACT group was divided into 4 subgroups according to the type of an anticoagulant: 1) VKA I (warfarin or acenocoumarol) for patients with an INR of 2 or higher on the day of the procedure; 2) VKA II for patients with an INR of less than 2 on the day of the procedure; 3) DOAC (rivaroxaban, apixaban, or dabigatran in renal dosing [edoxaban is not registered in our country]); and 4) LMWH (enoxaparin / dalteparin or nadroparin in weight‑adjusted dosing) (Figure 1). An antiplatelet agent was administered during the procedure. Anticoagulant agents were managed according to European Heart Rhythm Association [EHRA] recommendations. In patients with an intermediate and high risk of a thromboembolic event, VKA was administered perioperatively in patients with an INR of 3 or less (or 3.5 or less in patients with mechanical valve prosthesis), but in patients with a low thromboembolic risk, it was discontinued 3 to 4 days prior to the procedure.³ Treatment with DOAC was interrupted for 24 to 36 hours during the procedure, the duration depending on the drug type and renal function. Of note, patients in the LMWH subgroup were on chronic heparin treatment, and there were no patients on a bridging therapy with LMWH.

Written informed consent was obtained from each patient included in the study. The patients’ privacy was protected by the anonymization of all data. Exclusion criteria were pregnancy, refusal to sign the informed consent form, lead and / or device extraction surgery, diagnosed thrombophilia or thrombocytopenia, and inability to attend follow‑up visits for logistic reasons. The study protocol (Supplementary material) was in accordance with the Declaration of Helsinki and was approved by the bioethics committee of the Poznan University of Medical Sciences in Poznań, Poland (no. 613/15).

Significant bleeding complications

All patients were evaluated for SBCs occurring during hospitalization or during a 30‑day follow‑up. The complications included significant pocket hematoma (SPH) or significant bleeding (SB). Significant pocket hematoma was defined as a swelling and painful mass extending the margin of the generator, requiring surgical intervention and / or prolonging hospitalization for at least 24 hours after the CIED procedure due to interruption of ACT or APT. Significant bleeding was defined according to International Society on Thrombosis and Hemostasis criteria as fatal or symptomatic bleeding in a critical area (eg, pericardial or gastrointestinal) or any bleeding causing a decrease in hemoglobin concentrations of more than 1.24 mmol/l or leading to transfusion of 2 or more units of red blood cells.⁴

Statistical analysis

Patient characteristics were expressed as frequency (percentage) for categorical variables and medians (interquartile ranges) for continuous variables. None of the assessed parameters had a normal distribution as assessed using the Shapiro–Wilk test.

Categorical variables were compared using the 2‑tailed Fisher exact test or the χ² test as appropriate, and continuous variables were assessed using the Kruskal–Wallis analysis of variance test. A 2‑tailed α of 0.05 was considered significant.

Univariate logistic regression was used to evaluate the magnitude of association between potential risk factors and SBCs. A multivariable analysis was performed with selected variables that were significant in the univariate analysis. A P value of less than 0.05 was considered significant. In each model, the odds ratio (OR) for each independent variable was determined with a confidence interval (CI) of 95%. A receiver operating characteristic curve analysis was performed to determine the cutoff values for the predictive level of SBC development and for the evaluation of the models. Independent predictors were then assigned weighted points. The β regression coefficients were rounded to the nearest integer to derive weights (weighing scheme, Beta/integer), and the points were summed up across the predictors for a total score for each patient. The performance of the score in terms of SBC prediction was evaluated by the receiver operating characteristic curve analysis, and its predictive ability was determined by using c‑statistics as well as by calculation of the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, as well as positive and negative likelihood ratio for SBC development. All statistical analyses were performed using Statistica version 13.7 (StatSoft, Inc., Tulsa, Oklahoma, United States).

Predictors of serious bleeding complications

The results of the univariate and multivariable analyses for all potential predictors are presented in Table 3. The following characteristics were identified as independent predictors of SBCs: age ≥75 years (OR, 8.1; 95% CI, 3.54–18.54); CRT/ICD surgery (OR, 5.96; 95% CI, 2.48–14.32); upgrade procedure (OR, 10.22; 95% CI, 4.05–25.78); uncontrolled arterial hypertension (OR, 4.82; 95% CI, 1.78–13.06); presence of valvular prosthesis, either biological or mechanical (OR, 7.85; 95% CI, 3.15–19.58); current malignancy (OR, 6.11; 95% CI, 1.81–20.66); coexistence of renal failure (OR, 4.28; 95% CI, 1.86–9.87); and the use of antiplatelet drugs (clopidogrel [OR, 6.69; 95% CI, 2.48–18.04] or ticagrelor [OR, 22.25; 95% CI, 4.56–108.46]). It should be noted that the use of ticagrelor was the strongest risk factor.

The new PACE DRAP scoring system

Based on the SBC risk factors identified in the multivariable analysis, we propose a new simple score termed PACE DRAP. PACE DRAP is an acronym corresponding to each predictor: presence of valvular prosthesis (P), uncontrolled arterial hypertension (A); cancer (C); elderly (E); device type (D); renal failure (R); antiplatelets (A); and procedure type (P). The score was created using the weighted points proportional to the β regression coefficient rounded to the nearest integer in the multivariable analysis. The maximal score is 16 points. A detailed description of the factors that are included in the PACE DRAP acronym and the appropriate scoring are presented in Table 4. The PACE DRAP score significantly predicted the occurrence of SBCs (area under the curve [AUC], 0.95; P <0.001), and a score of 6 was identified as the cutoff point for high risk of SBCs with a sensitivity of 88.24% and a specificity of 87.23% (Figure 2).

Prognostic performance of the PACE DRAP score

Our analyses showed that the final PACE DRAP model had a discriminatory ability with an accuracy of 87.26%. Among the entire studied population, 178 patients were classified as having a high risk of SBCs, 44 of whom actually developed SBCs within 30 days after CIED surgery (PPV, 24.7%; NPV, 99.3%). The detailed predictive performance of the PACE DRAP score is presented in Table 5.

Significant bleeding complications

In this study, the frequency of SBCs in the entire population was quite low (4.5%). The reported incidence of SBCs varies widely, from 0.7% to 5.7%, with an increasing trend in recent years, which is probably associated with the high number of CIED procedures and an increasing percentage of more complex systems.^1,7,8 Another important reason may be patients’ longevity, which results in more frequent interventions in the elderly population, who are burdened with severe comorbidities, which may increase the risk of complications.

In this study, SBCs were most frequent in the TAT group. Patients in this group underwent CIED implantation within 2 months after an acute coronary incident or drug‑eluting stent implantation. Data on bleeding complications in patients receiving TAT are limited. However, other studies have shown an increased risk of bleeding, with no difference in the risk of a thromboembolic or cardiovascular event in patients receiving TAT compared with those receiving warfarin and clopidogrel.^9,10

Previous studies showed that periprocedural bridging therapy significantly increases the risk of pocket hematoma.⁸ One of the reasons for the increased incidence of SPHs in patients on LMWH seems to be postoperative use of heparin.¹¹ Although we demonstrated quite a high incidence of SPHs in the LMWH group (22%; 8 of 36 patients), the administration of heparin was not a significant risk factor in the multivariable analysis, probably due to a small number of patients receiving this form of ACT. According to current EHRA guidelines, the use of LMWH in the periprocedural period should be avoided in patients undergoing CIED surgery.³

The PACE DRAP score for risk assessment of significant bleeding complications

Procedure type (P)

We demonstrated that system upgrades increase the risk of SBCs 10‑fold. These results are consistent with previous literature data.²⁴ This can be explained by the additional dissection of fibrous tissue around the device during subsequent procedures, and greater manipulation of surrounding structures may cause damage of local blood vessels.²² Furthermore, implanting a new electrode may contribute to direct injury and disruption of the vein or heart wall, resulting in local bleeding or, in the event of major injury, tamponade. Our results, in combination with previous data, confirm that all types of reintervention are associated with a greater risk of complications compared with first‑time CIED surgery.

The simple PACE DRAP scoring system could be used as a quick and practical tool for SBCs risk estimation but requires external validation. Our internal validation showed that PACE DRAP was able to discriminate patients at high risk of SBCs with high accuracy, sensitivity, and specificity. However, other risk factors, such as the use of nonprescription drugs, should also be considered. It should be emphasized that several of the identified risk factors, such as hypertension, renal failure stage, or the use of antiplatelets, are potentially modifiable.

Study limitations

This study has several limitations, the main being its observational design, which prevented an equitable division of the analyzed group in terms of the type of APT and ACT used. The study included a small number of patients from a single center. Another important limitation is the heterogeneity of the analyzed group in terms of demographic and clinical characteristics, which could potentially affect the results. Although all the prescription drugs that affect the hemostatic system were included in our data set, the use of nonprescription drugs would have gone undetected. Bleeding episodes or other significant comorbidities only revealed in the primary care setting might not have been visible in our data set and may thus be underrepresented. Another limitation is that we could not validate the accuracy of the PACE DRAP scoring system using other cohorts.

Conclusions

We identified strong predictors of SBCs, several of which are potentially modifiable. We devised PACE DRAP, a simple bedside scoring system that may enable the identification of patients at high risk of SBCs related to CIED surgery without the need for laboratory testing.